Science-Informed Health Policies for Oral and Systemic Health.

Oral, dental and craniofacial (ODC) health has a profound impact on general health and welfare throughout life, yet US dentists and physicians operate across misaligned silos. This protracted division limits access to optimal health, supports fee for services, and exacerbates health disparities. Early in the 20th century, the most frequent dental therapy was tooth extraction: removed infected teeth were substituted by prosthetic appliances - commonly, dentures or nothing. Most adults assumed becoming edentulous was a normal corollary of aging. With the discovery of penicillin and other antibiotics, healthcare professionals and policy makers predicted infectious diseases would become irrelevant. However, given numerous health threats, including SARS-CoV-2, HIV, multidrug-resistant bacteria, Zika virus, Ebola virus, and now monkeypox, public and professional awareness of transmissible infectious diseases has never been more evident. Ironically, little attention has been paid to unmet transmissible, infectious, common oral diseases - dental caries and periodontal diseases. Therefore, these persist within "the silent and invisible epidemic". The preventable death of a young boy in 2007 from an infected untreated tooth that produced bacterial meningitis is a profound reminder that our nation has vast inequities in education, health, and welfare. The impact of oral infections on hospital-acquired pneumonia, post-operative infection in cardiac valve surgery, and even academic performances of disadvantaged children displayed through sociodemographic characteristics and access to care determinants also are profound! This paper asserts that current and emerging ODC health knowledge and science will inform health policies and advance equity in access to care, affordable costs, and optimal healthcare outcomes. We recommend that legal and regulatory systems and public health programs be required to ensure health equity. A fair healthcare system that addresses holistic healthcare must be transparent, accessible, integrated and provide a standard of oral healthcare based upon scientific evidence for all people across the lifespan.

From high definition precision healthcare to precision public oral health: opportunities and challenges.

In anticipation of a major transformation in healthcare, this review provides highlights that anticipate the near future for oral public health (and beyond). Personalized or precision healthcare reflects the expectation that advances in genomics, imaging, and other domains will extend our risk assessment, diagnostic, and prognostic capabilities, and enables more effective prevention and therapeutic options for all Americans. Meanwhile, the current healthcare system does not meet cost, access, or quality criteria for all Americans. It is now an imperative that the success of "smart," quality, and cost-effective high definition precision healthcare requires a public health perspective for several reasons: a) to enhance generalizability, b) to assess methods of implementation, and c) to focus on both risk and prevention in large and small populations, thereby providing a balance between the generation of long-term knowledge and short-term health gains. Sensitivity and resolution, reasonable cost, access to all Americans, coordinated comprehensive care, and advances in whole genome sequencing (WGS) and big data analyses, coupled to other advances in biotechnology and digital/artificial intelligence/machine learning devices, and the behavioral, social, and environmental sciences, offer remarkable opportunities to improve the health and wellness of the American people [genotype + phenotype + environment + behavior = high definition healthcare]. The opportunity is to significantly improve the well-being and life expectancy of all people across the lifespan including the least-advantaged people in our society and potentially increase access, reduce the national costs, and improve health outcomes.

A school-based public health model to reduce oral health disparities.

OBJECTIVES: Although dental decay is preventable, it remains the most common pediatric chronic disease. We describe a public health approach to implementing a scalable and sustainable school-based oral health program for low-income urban children. METHODS: The Los Angeles Trust for Children's Health, a nonprofit affiliated with the Los Angeles Unified School District, applied a public health model and developed a broad-based community-coalition to a) establish a District Oral Health Nurse position to coordinate oral health services, and b) implement a universal school-based oral health screening and fluoride varnishing program, with referral to a dental home. Key informant interviews and focus groups informed program development. Parent surveys assessed preventative oral health behaviors and access to oral health services. Results from screening exams, program costs and rates of reimbursement were recorded. RESULTS: From 2012 to 2015, six elementary schools and three dental provider groups participated. Four hundred ninety-one parents received oral health education and 89 served as community oral health volunteers; 3,399 screenings and fluoride applications were performed on 2,776 children. Sixty-six percent of children had active dental disease, 27 percent had visible tooth decay, and 6 percent required emergent care. Of the 623 students who participated for two consecutive years, 56 percent had fewer or no visible caries at follow-up, while only 17 percent had additional disease. Annual program cost was $69.57 per child. CONCLUSIONS: Using a broad based, oral health coalition, a school-based universal screening and fluoride varnishing program can improve the oral health of children with a high burden of untreated dental diseases.

The Impact of Research on the Future of Dental Education: How Research and Innovation Shape Dental Education and the Dental Profession.

Scientific inquiry and discovery are the fuel for education, research, technology, and health care in all the health professions: dentistry, medicine, nursing, pharmacy, and allied health sciences. The progression of discoveries from basic or fundamental to clinical research is followed by the progression from clinical to implementation and improved health outcomes and processes. Generally, implementation science is the scientific study of methods to promote the systematic uptake of research findings (e.g., basic, translational, behavioral, socioeconomic, and clinical) as well as other related evidence-based practices into standards of care, thereby improving the quality, effectiveness, and cost benefits of health care services. There is little doubt that science has and will continue to provide the essential fuel for innovations that lead to new and improved technologies for risk assessment, prevention, diagnosis, treatments and therapeutics, and implementation for addressing oral and craniofacial diseases and disorders. The history of the U.S. dental profession reviewed in this article gives testimony to the continued need for investments in scientific inquiry that accelerate progress in comprehensive health care for all people. This article was written as part of the project "Advancing Dental Education in the 21st Century."

Effects of Usag-1 and Bmp7 deficiencies on murine tooth morphogenesis.

BACKGROUND: Wnt5a and Mrfzb1 genes are involved in the regulation of tooth size, and their expression levels are similar to that of Bmp7 during morphogenesis, including during the cap and early bell stages of tooth formation. We previously reported that Usag-1-deficient mice form supernumerary maxillary incisors. Thus, we hypothesized that BMP7 and USAG-1 signaling molecules may play important roles in tooth morphogenesis. In this study, we established double genetically modified mice to examine the in vivo inter-relationships between Bmp7 and Usag-1. RESULTS: We measured the volume and cross-sectional areas of the mandibular incisors using micro-computed tomography (micro-CT) in adult Bmp7- and Usag-1-LacZ knock-in mice and their F2 generation upon interbreeding. The mandibular incisors of adult Bmp7+/- mice were significantly larger than those of wild-type (WT) mice. The mandibular incisors of adult Usag-1-/- mice were the largest of all genotypes examined. In the F2 generation, the effects of these genes were additive; Bmp7+/- was most strongly associated with the increase in tooth size using generalized linear models, and the total area of mandibular supernumerary incisors of Usag-1-/-Bmp7+/- mice was significantly larger than that of Usag-1-/-Bmp7 +/+ mice. At embryonic day 15 (E15), BrdU assays demonstrated that the labeling index of Bmp7+/- embryos was significantly higher than that of WT embryos in the cervical loop. Additionally, the labeling index of Usag-1-/- embryos was significantly the highest of all genotypes examined in dental papilla. CONCLUSIONS: Bmp7 heterozygous mice exhibited significantly increased tooth sizes, suggesting that tooth size was controlled by specific gene expression. Our findings may be useful in applications of regenerative medicine and dentistry.

A model for interprofessional health care: lessons learned from craniofacial teams.

Seventy-six years ago, Herbert K. Cooper, DDS, DSc, LHD, FACD, created the first interprofessional health care team in response to the frequency of craniofacial anomalies and related speech and hearing deficits in Lancaster, Pa. His experiences and those from subsequent "medical-dental-nursing-pharmacy allied health professions" craniofacial teams inform and provide "best practices" for the future of interprofessional education. This paper revisits the genesis of craniofacial teams and highlights successes, challenges and cost benefits applicable today.

Interactions between BMP-7 and USAG-1 (uterine sensitization-associated gene-1) regulate supernumerary organ formations.

Bone morphogenetic proteins (BMPs) are highly conserved signaling molecules that are part of the transforming growth factor (TGF)-beta superfamily, and function in the patterning and morphogenesis of many organs including development of the dentition. The functions of the BMPs are controlled by certain classes of molecules that are recognized as BMP antagonists that inhibit BMP binding to their cognate receptors. In this study we tested the hypothesis that USAG-1 (uterine sensitization-associated gene-1) suppresses deciduous incisors by inhibition of BMP-7 function. We learned that USAG-1 and BMP-7 were expressed within odontogenic epithelium as well as mesenchyme during the late bud and early cap stages of tooth development. USAG-1 is a BMP antagonist, and also modulates Wnt signaling. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced. Using explant culture and subsequent subrenal capsule transplantation of E15 USAG-1 mutant maxillary incisor tooth primordia supplemented with BMP-7 demonstrated in USAG-1+/- as well as USAG-1-/- rescue and supernumerary tooth development. Based upon these results, we conclude that USAG-1 functions as an antagonist of BMP-7 in this model system. These results further suggest that the phenotypes of USAG-1 and BMP-7 mutant mice reported provide opportunities for regenerative medicine and dentistry.

Evolution of the scientific basis for dentistry and its impact on dental education: past, present, and future.

Science is the fuel for technology and the foundation for understanding the human condition. In dental education, as in all health professions, science informs a basic understanding of development, is essential to understand the structure and function of biological systems, and is prerequisite to understand and perform diagnostics, therapeutics, and clinical outcomes in the treatment of diseases and disorders. During the last seventy-five years, biomedical science has transformed from discipline-based scientists working on a problem to multidisciplinary research teams working to solve complex problems of significance to the larger society. Over these years, we witnessed the convergence of the biological and digital revolutions with clinical health care in medical, dental, pharmacy, nursing, and allied health care professional education. Biomedical science informs our understanding, from human genes and their functions to populations, health disparities, and the biosphere. Science is a "way of knowing," an international enterprise, a prerequisite for the health professions, and a calling and adventure to the curious mind. Science, the activity of doing science, is in the national self-interest, in the defense of a nation, and critical to the improvement of the human condition. In the words of Vannevar Bush, "science is the endless frontier."

The primary site of the acrocephalic feature in Apert Syndrome is a dwarf cranial base with accelerated chondrocytic differentiation due to aberrant activation of the FGFR2 signaling.

Activation of osteoblastic bone anabolism in the calvarial sutures is considered to be the essential pathologic condition underlying mutant FGFR2-related craniofacial dysostosis. However, early clinical investigations indicated that abnormal cartilage development in the cranial base was rather a primary site of abnormal feature in Apert Syndrome (AS). To examine the significance of cartilaginous growth of the cranial base in AS, we generated a transgenic mouse bearing AS-type mutant Fgfr2IIIc under the control of the Col2a1 promoter-enhancer (Fgfr2IIIc(P253R) mouse). Despite the lacking expression of Fgfr2IIIc(P253R) in osteoblasts, exclusive disruption of chondrocytic differentiation and growth reproduced AS-like acrocephaly accompanied by short anterior cranial base with fusion of the cranial base synchondroses, maxillary hypoplasia and synostosis of the calvarial sutures with no significant abnormalities in the trunk and extremities. Gene expression analyses demonstrated upregulation of p21, Ihh and Mmp-13 accompanied by modest increase in expression of Sox9 and Runx2, indicating acceleration of chondrocytic maturation and hypertrophy in the cranial base of the Fgfr2IIIc(P253R) mice. Furthermore, an acquired affinity and specificity of mutant FGFR2IIIc(P253R) receptor with FGF2 and FGF10 is suggested as a mechanism of activation of FGFR2 signaling selectively in the cranial base. In this report, we strongly suggest that the acrocephalic feature of AS is not alone a result of the coronal suture synostosis, but is a result of the primary disturbance in growth of the cranial base with precocious endochondral ossification.

Scientific investments continue to fuel improvements in oral health (May 2000-present).

The release of Oral Health in America: A Report of the Surgeon General in May 2000 raised national, state, and local awareness, for the first time ever, of the impact of oral disease in America. The report emphasized oral health's link to general health and well-being, and called for a national effort among individuals, communities, and health care providers to improve oral health among all Americans. One of the objectives from the Surgeon General's Report On Oral Health was to "advance the science base and translate into practice." Our objective here is to address how the science base has progressed in 3 main areas that have significant potential to impact oral health: sequencing of the human genome, tissue engineering, and saliva diagnostics. A secondary objective is to comment on progress in our understanding of dental caries and its impact on young children.

Science is the fuel for the engine of technology and clinical practice.

BACKGROUND: The biological, chemical, behavioral and physical sciences provide the fuel for innovation, discovery and technology that continuously improves the quality of the human condition. Computer power derived from the dramatic breakthroughs of the digital revolution has made extraordinary computational capacity available for diagnostic imaging, bioinformatics (the science of information) and numerous aspects of how we practice dentistry in the 21st century. OVERVIEW: The biological revolution was initiated by the identification of the structure for DNA in 1953, a discovery that continues to catalyze improvements in patient care through new and better diagnostics, treatments and biomaterials. Humanity's most basic and recognizable characteristics--including the face--are now better understood through the elucidation of our genome and proteome, the genes and proteins they encode. Health care providers are beginning to use personalized medicine that is based on a person's genetic makeup and predispositions to disease development. CONCLUSIONS: Advances in the fields of genetics, developmental and stem cell biology, and many other disciplines continue to fuel innovative research findings that form the basis for new diagnostic tests, therapeutic interventions and procedures that improve the quality of life for patients. Scientists are on the threshold of applying knowledge in stem cell biology to regenerative medicine and dentistry, heralding an era when clinicians can consider using biological engineering to replace tissues and organs lost to disease or trauma.

What the future holds for ectodermal dysplasias: future research and treatment directions.

A contrarian view suggests that the ectodermal dysplasias, including more than 200 different disorders, represent clinical variability and molecular heterogeneity as well as complex multigene heritable conditions often characterized by dysmorphogenesis of derivatives of embryonic ectoderm and beyond. Controversy exists over which syndromes do or do not belong in the classification of the clinical features that characterize ectodermal dysplasias. For example, Ellis-van Creveld syndrome is characterized by abnormalities of the teeth and hair, as well as of the skeleton and the cardiovascular system. Precision in diagnosis often is a preamble for improved patient diagnosis, treatment and desired outcomes. In tandem, molecular studies of complex epithelial-mesenchymal interactions required for ectodermal derivatives (e.g., hair, nail, skin, teeth, and exocrine glands) continue to identify and explain many signal transduction pathways and networks related to ectodermal dysplasias. Meanwhile, major international investments in fundamental biomedical research continue to yield significant benefits to the larger society. The convergence of informatics, nanotechnology, genomics, and epigenetic studies with clinical medicine and dentistry promise major progress for special needs patients such as ectodermal dysplasias. For example, investments in the molecular biology of genes and their regulation and function now provide more than 30 candidates for specific biomarkers to improve diagnosis, prognosis, treatments, therapeutics, and biomaterials for ectodermal dysplasias. Innovations in high throughput genotyping, gene mapping, single nucleotide polymorphisms (SNPs), interference RNA treatments, bioimaging, tissue engineering and related biomimetic approaches to design and fabricate biomaterials, offer enormous promise for the future of ectodermal dysplasias.

Fate of HERS during tooth root development.

Tooth root development begins after the completion of crown formation in mammals. Previous studies have shown that Hertwig's epithelial root sheath (HERS) plays an important role in root development, but the fate of HERS has remained unknown. In order to investigate the morphological fate and analyze the dynamic movement of HERS cells in vivo, we generated K14-Cre;R26R mice. HERS cells are detectable on the surface of the root throughout root formation and do not disappear. Most of the HERS cells are attached to the surface of the cementum, and others separate to become the epithelial rest of Malassez. HERS cells secrete extracellular matrix components onto the surface of the dentin before dental follicle cells penetrate the HERS network to contact dentin. HERS cells also participate in the cementum development and may differentiate into cementocytes. During root development, the HERS is not interrupted, and instead the HERS cells continue to communicate with each other through the network structure. Furthermore, HERS cells interact with cranial neural crest derived mesenchyme to guide root development. Taken together, the network of HERS cells is crucial for tooth root development.

Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse.

Uterine sensitization associated gene-1 (USAG-1) is a BMP antagonist, and also modulates Wnt signaling. We previously reported that USAG-1 deficient mice have supernumerary teeth. The supernumerary maxillary incisor appears to form as a result of the successive development of the rudimentary upper incisor. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. We confirmed that BMPs were expressed in both the epithelium and mesenchyme of the rudimentary incisor at E14 and E15. BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced. Wnt signaling as demonstrated by the nuclear localization of beta-catenin was also up-regulated. Inhibition of BMP signaling rescues supernumerary tooth formation in E15 incisor explant culture. Based upon these results, we conclude that enhanced BMP signaling results in supernumerary teeth and BMP signaling was modulated by Wnt signaling in the USAG-1 deficient mouse model.

Rudiment incisors survive and erupt as supernumerary teeth as a result of USAG-1 abrogation.

The term "supernumerary teeth" describes production of more than the normal number of teeth in the primary or permanent dentitions. Their aetiology is not understood. Uterine sensitization associated gene-1 (USAG-1) is a BMP antagonist that plays important roles in the local regulation of BMP signaling by binding and neutralizing BMP activities, and also serves as a modulator of Wnt signaling. We report here that USAG-1 deficient mice have supernumerary teeth. The supernumerary maxillary incisor appears to form as a result of the successive development of the rudimentary upper incisor tooth. We confirmed that the USAG-1 expression is localized to the epithelium and mesenchyme of the rudimentary maxillary incisor tooth organ formation. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. Based upon these results, we conclude that USAG-1 controls the number of teeth in the maxillary incisor region by regulating apoptosis.

Incorporating leadership knowledge and skills into the dental education community.

Leadership has been studied for the past four decades with an emphasis upon leadership and the transformation of various cultures, especially within the private sector. It is also becoming evident that leaders and leadership skills are often derived from core personal values and perceptions of what is and what could be. This summary describes an eleven-week selective course termed "Dean's Leadership Course" at the School of Dentistry at the University of Southern California. This selective course (a non-credit elective learning opportunity outside the formal curriculum) recruits a modest team of learners consisting of faculty, staff, and students and approaches leadership within the context of a "learning organization" coupled with case-based and problem-based learning. At the conclusion of this eleven-week course, participants are granted continuing education credit. This summary encourages others in dental education to consider the compelling opportunity to nurture and cultivate leadership within the university dental school environs.